Sinensetin (SIN for short) is one of the most common polymethoxyflavonoids found in citrus fruits. Recently, it has been extensively studied due to its ability to prevent or treat a wide range of diseases, including diabetes, obesity, neurological disorders, and cancer. Oxidative stress is closely related to the pathogenesis of many diseases. Based on literature research and the results of our previous experiments, we found that flavonoids have significant antioxidant effects. This study found that sinensetin alleviated AAPH-induced oxidative stress in zebrafish and alleviated intestinal and brain damage (including brain neurons, vascular development, and blood-brain barrier integrity). This study is of great significance for further study of the relationship between gut-brain changes and oxidative stress. This study provides a practical and convenient tool for real-time tracking of the protective effect of natural products on the in vivo oxidative stress model induced by AAPH. In addition, it paves the way for the discovery of more antioxidants in the future.